Effects of selective and nonselective beta-adrenergic blockade on mechanisms of exercise conditioning.

Abstract

Exercise conditioning involves adaptations in the heart, peripheral circulation, and trained skeletal muscle that result in improved exercise capacity. Since the specific influence of /3-adrenergic stimulation on these various adaptations has not been clear, we studied the effect of 3,1-selective and nonselective ,B-adrenergic blockade on the exercise conditioning response of 24 healthy, sedentary men after an intensive 6 week aerobic training program. Subjects randomly assigned to receive placebo, 50 mg bid atenolol, or 40 mg bid nadolol were tested before and after training both on and off drugs. Comparable reductions in maximal exercise heart rate occurred with atenolol and nadolol, indicating equivalent /I-adrenergic blockade. Vascular 132-adrenergic selectivity was maintained with atenolol as determined by calf plethysmography during intravenous infusion of epinephrine. All subjects trained at greater than 85% of maximal heart rate and 80% of 'V02max determined on drug. \02max increased after training 16 + 2% (p < .05) in the placebo group and 6 2% (p < .05) in the atenolol group, while there was no change in the nadolol group. At maximal exercise, subjects receiving placebo increased their exercise duration and oxygen pulse significantly greater than those receiving atenolol or nadolol. During submaximal exercise there were reductions in heart rate and heart rate-blood pressure product in all three groups, but these reductions were greater with placebo than with either drug. Leg blood flow during submaximal exercise decreased 24 + 2% (p < .01) in the placebo group but was unchanged in the atenolol and nadolol groups. Lactates in arterialized blood during submaximal exercise were reduced equivalently in all three groups after training. Capillary/fiber ratio in vastus lateralis muscle biopsy specimens increased 31 ± 6% in the placebo group and 21 + 6% in the atenolol group (both p < .05) and tended to increase in the nadolol group. Succinic dehydrogenase and cytochrome oxidase activities in muscle biopsy specimens increased equivalently in all three groups after training. Thus, although exercise conditioning developed to some extent in both drug groups, especially during submaximal exercise, these changes were less marked than that with placebo. While /3-adrenergic blockade attenuated the exercise conditioning response, skeletal muscle adaptations including increases in oxidative enzymes, capillary supply, and decreases in exercise blood lactates were unaffected. Cardiac and peripheral vascular adaptations do appear to be affected by ,3-adrenergic blockade during training. Cardioselectivity does not seem to be important in modifying these effects. Circulation 74, No. 4, 664-674, 1986. AEROBIC EXERCISE TRAINING results in improved function of the heart, peripheral circulation, and skeletal muscle that results in enhanced physical work capacity. [1][2][3][4][5][6] The relative importance of each adaptation and the factors that separately or together in-

Effects of exercise training on mitochondrial function in patients with type 2 diabetes

“…Subjects receiving placebo improved maximal oxygen uptake to a higher extent than the two groups receiving medication, but all groups improved maximal oxygen uptake from baseline. Furthermore mitochondrial content increased in all three groups after training, but again the placebo-group improved to a higher extent [63] . Similar results were reported by Svedenhag et al [64] in young healthy subjects after 8 wk of endurance training.…”

“…An increased mitochondrial content (mtD-NA) was seen after training in both groups, accompanied by a similar intrinsic mitochondrial function before and after training in both groups [17] , indicating that mitochondrial OXPHOS capacity was increased to a similar extent and an increase in mitochondrial content (succinyl dehydrogenase activity) in the placebo and the metoprolol group, whereas no improvements after training was seen with propranolol [62] . Another group investigated 6 wk of endurance training in healthy young subjects [63] . The subjects were randomized to either a selective (atenolol) or nonselective (nadolol) β-adrenergic blocker or placebo.…”

Acute β-adrenergic stimulation does not alter mitochondrial protein synthesis or markers of mitochondrial biogenesis in adult men

“…We used a study design that allowed us to avoid complications in relation to administration and withdrawal of medication. The conflicting data of Wolfel et al (64) and Svedenhag et al (56) could be explained by the fact that the former measured V O 2 max at four time-points, before and after training, while participants were receiving or had stopped the drug treatment, while the latter measured before and 4 days after the secession of drug treatment and exercise training. As previously discussed, increased ␤-AR sensitivity can occur following treatment with ␤-AR blockers (11,12,35); thus, differences in reported training effects may be influenced by the timing of measurements around drug treatments and whether the participants are consuming the drugs while measurements are made.…”

“…In mice, ␤-ARs appear to play an important role in the regulation of skeletal muscle mitochondrial biogenesis (17,30), whereas data from humans are less clear (25,48,56,62,64). Accordingly, we have investigated the hypothesis that acute intravenous ␤-AR stimulation would increase skeletal muscle mitochondrial biogenesis in adult humans.…”

“…Specific to skeletal muscle adaptations, ␤-AR blockade during endurance training showed a blunted increase on maximal activity of selected oxidative enzymes (56,64). Additionally, hypertensive adults receiving ␤ 1 -AR selective or nonselective blockers had blunted training effects in maximal exercise capacity (V O 2 max ) compared with placebo (1).…”